Defensins: Natural component of human innate immunity

The widespread use of antibiotics has contributed to a huge increase in the number of resistant bacteria. New classes of drugs are therefore being developed of which defensins are a potential source. Defensins are a group of antimicrobial peptides found in different living organisms, involved in the first line of defense in their innate immune response against pathogens. This review summarizes the results of studies of this family of human antimicrobial peptides (AMPs). There is a special emphasis on describing the entire group and individual peptides, history of their discovery, their functions and expression sites. The results of the recent studies on the use of the biologically active peptides in human medicine are also presented. The pharmaceutical potential of human defensins cannot be ignored, especially considering their strong antimicrobial activity and properties such as low molecular weight, reduced immunogenicity, broad activity spectrum and resistance to proteolysis, but there are still many challenges and questions regarding the possibilities of their practical application.     

经乳晕隐痕切口在胸外科男性患者微创手术中的应用

 目的 探讨经乳晕隐痕切口在胸外科男性患者微创胸腔镜手术中的可行性和优势。方法 回顾性分析2016-03至2019-01武警海警总队医院胸心外科收治的单孔胸腔镜手术男性患者资料,其中56例经乳晕切口(乳晕组),68例常规切口(对照组)。比较两组患者手术时间、术中出血量、术后胸腔引流量、拔管时间、术后住院天数、术后第1天和第2天的视觉模拟评分,以及术后1、3个月切口不适情况、远期切口满意度等。结果 所有患者均顺利完成手术,术中术后均未出现严重并发症。两组在手术时间、术中出血量、术后胸腔引流液量、拔除胸管时间、术后住院天数、术后第1天VAS评分等方面差异无统计学意义,与对照组相比,乳晕组的术后第2天VAS评分下降明显(P＜0.05),切口不适人数减少,差异有统计学意义(P＜0.05)。术后6个月随访乳晕组对瘢痕非常满意者有41例(73.2%),对照组有19例(27.9%),两组瘢痕满意度比较,差异有统计学意义(P＜0.05)。结论 在部分胸部疾病中,男性患者选择经乳晕切口行单孔胸腔镜手术是安全、可行的,可以提高切口满意度,更能体现出微创无瘢痕这一特点,值得临床推广。     

Pathogenic microbes manipulate cofilin activity to subvert actin cytoskeleton

Abstract

Actin-depolymerizing factor (ADF)/cofilin proteins are key players in controlling the temporal and spatial extent of actin dynamics, which is crucial for mediating host–pathogen interactions. Pathogenic microbes have evolved molecular mechanisms to manipulate cofilin activity to subvert the actin cytoskeletal system in host cells, promoting their internalization into the target cells, modifying the replication niche and facilitating their intracellular and intercellular dissemination. The study of how these pathogens exploit cofilin pathways is crucial for understanding infectious disease and providing potential targets for drug therapies.     

Predicting the Functional,Molecular, and Phenotypic Consequences of Amino Acid Substitutions using Hidden Markov Models

The rate at which nonsynonymous single nucleotide polymorphisms (nsSNPs) are being identified in the human genome is increasing dramatically owing to advances in whole‐genome/whole‐exome sequencing technologies. Automated methods capable of accurately and reliably distinguishing between pathogenic and functionally neutral nsSNPs are therefore assuming ever‐increasing importance. Here, we describe the Functional Analysis Through Hidden Markov Models (FATHMM) software and server: a species‐independent method with optional species‐specific weightings for the prediction of the functional effects of protein missense variants. Using a model weighted for human mutations, we obtained performance accuracies that outperformed traditional prediction methods (i.e., SIFT, PolyPhen, and PANTHER) on two separate benchmarks. Furthermore, in one benchmark, we achieve performance accuracies that outperform current state‐of‐the‐art prediction methods (i.e., SNPs&GO and MutPred). We demonstrate that FATHMM can be efficiently applied to high‐throughput/large‐scale human and nonhuman genome sequencing projects with the added benefit of phenotypic outcome associations. To illustrate this, we evaluated nsSNPs in wheat (Triticum spp.) to identify some of the important genetic variants responsible for the phenotypic differences introduced by intense selection during domestication. A Web‐based implementation of FATHMM, including a high‐throughput batch facility and a downloadable standalone package, is available at http://fathmm.biocompute.org.uk .     

微小RNA介导的牙周炎与动脉粥样硬化相关机制的研究进展

牙周炎是一种主要由菌斑生物膜所引起的牙周支持组织慢性炎症破坏性疾病,与宿主的免疫反应相关。牙周致病菌可通过一过性菌血症进入血液循环系统,引发血管炎症反应,增加心血管疾病患病风险。微小RNA(microRNA)作为近年来小分子RNA的研究热点,可在表观遗传学水平调控基因表达,参与炎症调节。本文综述了牙周致病菌通过microRNA调控免疫炎症反应的机制,从而介导动脉粥样硬化的发生、发展,为牙周炎与动脉粥样硬化疾病关联的分子机制研究提供新的思路。此外,通过探索动脉粥样硬化与牙周炎相关特异性microRNA的表达模式,可为未来诊断或治疗心血管疾病提供新的参考。